Human Physiology, 14th edition (2016)

426 Chapter 13

potentials. The majority of myocardial cells have resting mem-

brane potentials of about 2 85 mV. When stimulated by action

potentials from a pacemaker region, these cells become depo-

larized to threshold, at which point their voltage-regulated Na^1

gates open. The upshoot phase of the action potential of non-

pacemaker cells is due to the rapid inward diffusion of Na^1

through fast Na 1 channels. Following the rapid reversal of the

membrane polarity, the membrane potential quickly declines

to about 2 15  mV. Unlike the action potential of other cells,

however, this level of depolarization is maintained for 200 to

300 msec before repolarization ( fig. 13.19 ). This plateau phase

results from a slow inward diffusion of Ca^2 1 through slow Ca 2 1

channels, which balances a slow outward diffusion of K^1.

Rapid repolarization at the end of the plateau phase is achieved,

as in other cells, by the opening of voltage-gated K^1 channels

and the rapid outward diffusion of K^1 that results.

The long plateau phase of the myocardial action potential

distinguishes it from the spike-like action potentials in axons

channels in the sarcoplasmic reticulum (also called ryanodine
receptors; chapter 12, section 12.2) in a process of Ca 2 1 -induced
Ca 2 1 release (chapter 12; see fig. 12.34). This produces a massive
release of Ca^2 1 from the sarcoplasmic reticulum that causes con-
traction of the myocardial cells. Repolarization is then produced
by the opening of voltage-gated K^1 channels ( fig. 13.18 ).
When repolarization is complete, the mechanisms responsible
for the next diastolic depolarization begin, leading to the next action
potential and the next heartbeat. This produces a cardiac rate that
can vary depending on the effects of the autonomic nervous sys-
tem. Epinephrine and norepinephrine cause the production of cyclic
AMP within the pacemaker cells (chapter 11; see fig. 11.8), which
opens HCN channels for Na^1 to produce a depolarization. Produc-
tion of cAMP also promotes the entry of Ca^2 1 into the cytoplasm
through Ca^2 1 channels. By these means, sympathoadrenal stimula-
tion increases the rate of diastolic depolarization to help produce a
faster cardiac rate (chapter 14; see fig. 14.1), while also increasing
the strength of myocardial contraction (chapter 14; see fig. 14.2).
Acetylcholine (ACh), released by parasympathetic axons that inner-
vate the pacemaker cells, bind to their muscarinic receptors in the
plasma membrane. Acting through G-proteins, this causes the open-
ing of K^1 channels (chapter 9; see fig. 9.11). The outward diffu-
sion of K^1 slows the time required for the diastolic depolarization
to reach threshold, slowing the production of action potentials and
thereby slowing the cardiac rate.
Recent research suggests that the SA node is not a uniform
structure, but instead consists of different pacemaker regions that
are electrically separated from each other and from the surround-
ing myocardial cells of the right atrium. These regions communi-
cate electrically through different sinoatrial conduction pathways.
Action potentials spread through the sinoatrial conduction path-
ways to depolarize both atria and, through other conduction path-
ways (AV node, bundle of His, and Purkinje fibers), to depolarize
the ventricles. In this way, a region of the sinoatrial node paces the
heart to produce what is called a normal sinus rhythm.
As previously mentioned, the AV node and Purkinje fibers
can potentially serve as pacemakers but are normally sup-
pressed by action potentials originating in the SA node. This is
because when a membrane is producing an action potential, it
is in a refractory period (see fig. 13.21 ). When the membrane
of a cell other than a pacemaker cell recovers from its refrac-
tory period, it will again be stimulated by action potentials
from the SA node. This is because the diastolic depolarization
and action potential production in the SA node are faster than
in these other sites. If conduction from the SA node is blocked,
cells in one of these regions could spontaneously depolarize
and produce action potentials. This region would then serve
as an abnormal pacemaker, called an ectopic pacemaker or
ectopic focus. Because the normal SA node pacemaker has the
fastest spontaneous cycle, the rate set by an ectopic pacemaker
would usually be slower than the normal sinus rhythm.

Myocardial Action Potential

Once another myocardial cell has been stimulated by action
potentials originating in the SA node, it produces its own action

Figure 13.19 An action potential in a myocardial

cell from the ventricles. The plateau phase of the action

potential is maintained by a slow inward diffusion of Ca^2 1. The

cardiac action potential, as a result, is about 100 times longer in

duration than the spike-like action potential in an axon.

Millivolts

+ 20

• 20
  
  
  • 40
  
  
  • 60
  
  
  • 80
  
  
  
  


• 100

0

Milliseconds

500 100 150 200 250 300 350 400

K+Out

Na+In

Ca2+In (slow)

CLINICAL APPLICATION

Arrhythmias are abnormal patterns of electrical activity that

result in abnormalities of the heartbeat. Drugs used to treat

arrhythmias affect the nature and conduction of cardiac

action potentials, and have been classified into four differ-

ent groups. Group 1 drugs are those that block the fast Na^1

channels ( quinidine, procainamide, lidocaine ); group 2 drugs

are beta-blockers, interfering with the ability of catechol-

amines to stimulate beta-adrenergic receptors ( propranolol,

atenolol ); group 3 drugs block K^1 channels ( amiodarone ),

slowing repolarization; and group 4 drugs block the slow

Ca^2 1 channels ( verapamil, diltiazem ). Different arrhythmias

are best treated by the specific actions of each drug.